Detection of t(8;21) by reverse transcriptase polymerase chain reaction in patients in remission of acute myeloid leukaemia type M2 after chemotherapy or bone marrow transplantation

Saunders, Melanie J.; Tobal, Khalid; Yin, John

doi:10.1016/0145-2126(94)90100-7

Cited by 43 publications

(32 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…32,33 However, other data emphasized that patients not achieving a molecular remission after BMT could suffer from a higher rate of leukemic relapse compared to those with a negative RT-PCR test. [34][35][36] We and others 24 have shown that eliminated expression of AML1/ETO fusion transcripts after DLI was associated with a sustained and persistent complete molecular remission. The efficiency of inducing an anti-leukemic effect by DLI in t(8;21) AML relapse post-graft could be related to immunogenicity of peptide(s) derived from the fusion protein created by the leukemia-specific chromosomal translocation.…”

Section: Discussionmentioning

confidence: 97%

Extramedullary relapse after favorable molecular response to donor leukocyte infusions for recurring acute leukemia

et al. 1998

View full text Add to dashboard Cite

Donor leukocyte infusions (DLI) have turned out to be an efficient way to re-establish complete remission (CR) in chronic myeloid leukemia (CML) patients relapsing after allogeneic bone marrow transplantation (BMT). In these patients, absence of PCR bcr-abl fusion transcripts confirmed the potency of donor leukocytes to induce molecular response in relapsed CML. This ensured sustained remission and long-term survival. In this study, the capacity of DLI to induce molecular remission in acute leukemia relapse after BMT was analyzed. The results showed that following DLI, leukemic cell eradication gradually occurred over a prolonged time period. The time to complete disappearance of the molecular marker of the disease was 30 weeks in RT-PCR analysis. A sustained and persistent elimination of an AML1/ETO-positive leukemic clone in an AML-M 2 patient was observed. In contrast, an AML-M 5 with t(11;19) and an E2A/PBX1-positive ALL achieving cytogenetic and molecular bone marrow CR developed following DLI unusual sites of extramedullary leukemia relapse, despite continued bone marrow remission. This study adds further proof of the benefit of donor cell therapy in acute leukemia but shows that complete leukemic cell eradication appears to require a critical interval in order to establish effective immune responses at all sites where leukemic cells persist.

show abstract

Section: Discussionmentioning

confidence: 97%

Extramedullary relapse after favorable molecular response to donor leukocyte infusions for recurring acute leukemia

et al. 1998

View full text Add to dashboard Cite

show abstract

“…Analysis of the transcripts of t(8;21) leukemic cells demonstrated that MTG8 was fused either in-frame (Erickson et al, 1992;Nisson et al, 1992;Nucifora et al, 1993;Era et al, 1995a,b) or out-of-frame (Tighe and Calabi, 1994;van de Locht et al, 1994;Saunders et al, 1996) with the 5' region of AML1. Thus, in leukemic cells MTG8 is expressed as a part of the chimeric AML1/MTG8 protein(s).…”

Section: Introductionmentioning

confidence: 99%

Subcellular localization of the oncoprotein MTG8 (CDR/ETO) in neural cells

et al. 1998

View full text Add to dashboard Cite

The t(8;21) translocation associated with acute myeloid leukemia (AML) disrupts two genes, the AML1 gene also known as the core binding factor A2 (CBFA2) on chromosome 21, and a gene on chromosome 8, hereafter referred to as MTG8, but also known as CDR and ETO. Extensive information is available on AML1, a member of the CBF family of transcription factors, containing a highly conserved domain, the runt box, of the Drosophila segmentation gene runt. This gene is essential for the hematopoietic development and is found disrupted in several leukemias. In contrast, the function of the MTG8 gene is poorly understood. The predicted protein sequence shows two unusual, putative zinc-®ngers, three proline-rich regions, a PEST domain and several phosphorylation sites. In addition, we found a region encompassing aa 443 ± 514 predicted to have a signi®cant propensity to form coiled coil structures. MTG8 displays a high degree of similarity with nervy, a homeotic target gene of Drosophila, expressed in the nervous system. Human and mouse wild-type MTG8 are also highly expressed in brain relative to other tissues. For these reasons, we set out to investigate the expression and subcellular localization of the MTG8 protein in neural cells. Immunohistochemical experiments in a 12.5-dayold mouse embryo clearly showed that the protein was expressed in the neural cells of the developing brain and the spinal cord. In primary cultures of hippocampal neurons of 2 ± 3 day-old mice, MTG8 was found in the nucleus, in the cytoplasm and as ®ne granules in the neurites. Cytoplasmic localization of the protein was observed in Purkinje cells of both human and mouse cerebellum. The molecular mass of MTG8 in total human and mouse brain was analysed by immunoblotting and determined to be between 70 and 90 kDa. Isoforms with the same molecular mass were demonstrated in synaptosomes isolated from mouse forebrain. The evidence of MTG8 in the nucleus and cytoplasm of neural cells suggests a speci®c mechanism regulating the subcellular localization of the protein.

show abstract

“…It was previously shown that AML1-ETO fusion transcripts remain detectable throughout the course of therapy and even in patients in long-term remission. [4][5][6][7][8][9][10][11] Although this persistence of AML1-ETO is observed in long-term survivors, it seems obvious that it is residual leukemia that is responsible for relapse. The advent of modern real-time PCR techniques has enabled to quantify accurately residual leukemia and thus has provided deeper insight in the response to therapy and the dynamics of residual leukemic blasts.…”

Section: Introductionmentioning

confidence: 99%

The quality of molecular response to chemotherapy is predictive for the outcome of AML1-ETO-positive AML and is independent of pretreatment risk factors

et al. 2007

View full text Add to dashboard Cite

The outcome of 45 AML1-ETO-positive acute myeloid leukemia (AML) patients was analyzed with special emphasis on the quality of molecular response to therapy. Patients received double induction therapy, either 6-thioguanine, cytarabine, and daunorubicin (TAD9)/high-dose cytosine arabinoside plus mitoxantrone (HAM) or HAM/HAM, followed by consolidation therapy (TAD9) according to the AML-Cooperative group 92 trial (AMLCG92) and AML-Cooperative group 99 trial (AMLCG99). All cases underwent cytomorphological, cytogenetical and molecular genetic analyses. AML1-ETO transcript levels were quantitatively assessed at diagnosis and during follow-up by real-time reverse transcriptase-polymerase chain reaction (RT-PCR). The median reduction of initial AML1-ETO expression level was 4 log (range 0-5) after both induction and consolidation therapies. The quality of molecular response after induction as well as consolidation therapies had significant impact on the cumulative incidence of relapse (P ¼ 0.021 and P ¼ 0.001, respectively), event free survival (EFS: P ¼ 0.001 and P ¼ 0.001, respectively) and overall survival (OS: P ¼ 0.013 and P ¼ 0.014, respectively). HAM/HAM improved the molecular response to induction therapy (P ¼ 0.042) but after consolidation, no differences in molecular response were detectable between TAD9/HAM and HAM/HAM. Patient-or disease-related factors had no impact on the molecular response to induction or consolidation therapy. The current study demonstrates that quantification of AML1-ETO transcript levels is a powerful tool for prediction of prognosis that is independent of pretreatment risk factors, and may be helpful for directing therapeutic decisions in the future.

show abstract

Detection of t(8;21) by reverse transcriptase polymerase chain reaction in patients in remission of acute myeloid leukaemia type M2 after chemotherapy or bone marrow transplantation

Cited by 43 publications

References 8 publications

Extramedullary relapse after favorable molecular response to donor leukocyte infusions for recurring acute leukemia

Extramedullary relapse after favorable molecular response to donor leukocyte infusions for recurring acute leukemia

Subcellular localization of the oncoprotein MTG8 (CDR/ETO) in neural cells

The quality of molecular response to chemotherapy is predictive for the outcome of AML1-ETO-positive AML and is independent of pretreatment risk factors

Contact Info

Product

Resources

About